The end of the era of estrogen

April 13, 2011

Scores of observational studies done in the 1970s and ’80s supported the view that estrogen is protective against heart disease. These studies were so overwhelming that in 1990 Wyeth-Ayerst, the leading maker of estrogen petitioned the Food and Drug Administration to approve Premarin, its estrogen drug, for the prevention of heart disease in postmenopausal women. The FDA advisory committee recommended such approval.

However, the National Women’s Health Network, a women’s advocacy group that refuses money from the drug industry as part of its charter, vehemently opposed approval on the grounds that observational studies do not constitute proof. Observational studies show a relationship between lifestyle factors and diseases in populations. But there are so many different factors involved in the lifestyles and environments of populations and groups that it is impossible to determine which of them is a cause in the prevention of a disease or in its promotion. In the observational studies done on hormone replacement therapy (HRT), the women on HRT might have had healthier lifestyles than the women not on HRT. Their healthier lifestyles could have been protecting them from heart disease, not the hormone replacement therapy.

The National Women’s Health Network also argued that no drug to prevent heart disease in men had ever been approved without a randomized, double blind placebo controlled trial, the gold standard of scientific evidence.

A tale Of two studies

On the basis of these objections, the FDA made the unusual move of rejecting the near-unanimous recommendation of its advisory committee and made approval of estrogen as a heart protecting drug contingent upon proof in a randomized, clinical trial. To meet this demand, Wyeth-Ayerst Laboratories financed the Heart and Estrogen/Progestin Replacement Study, known as HERS, in the hopes of being able to advertise its drug Prempro as a preventive and treatment for heart disease.

HERS was a randomized clinical trial conducted among 2,763 postmenopausal women who already had coronary heart disease, a group in whom effects would be easier to find. Its purpose was to assess the benefits and risks of Prempro, the most commonly used combined hormone preparation in the United States.

At the same time, in response to lobbying by women’s groups, Congress appropriated money for the Women’s Health Initiative, WHI, a huge and expensive randomized clinical trial of 27,000 predominantly healthy women to be conducted by the National Institutes of Health. One arm of the WHI involved 16,000 of these women who were randomly assigned to take Prempro or a placebo.

The results

In July of 2002, the results of the HERS study and the Prempro arm of the WHI study were reported in the Journal of the American Medical Association. What they found:

In the HERS study, HRT did not prevent heart attacks; hormone users had a doubling of the risk of blood clots in the legs and lungs; the rate of gallbladder disease needing surgery increased by about 45 percent; and daily hormone use was associated with a worsening of urinary incontinence.

In the WHI study, there was an increase in coronary heart disease, in strokes, in pulmonary embolisms (blood clots in the lungs), in deep vein thrombosis (blood clots in the legs), and in invasive breast cancer, which was more advanced and harder to treat. A spin-off study of the WHI found that HRT doubles the risk of Alzheimer’s disease and other types of dementia in women 65 and older. The WHI did show a decrease in osteoporotic fractures and colorectal cancers for women taking HRT.

The bottom line? The risks of HRT outweigh the benefits. Most of the diseases it was thought to prevent it were found to cause. HERS and WHI are two landmark studies marking the end of the era of estrogen as a panacea for postmenopausal women.

Mary Lou Williams, M. Ed., is a lecturer and writer in the field of nutrition. She welcomes inquiries. She can be reached at 267-6480.